Noroxymorphone is a morphinan intermediate useful for making a series of biologically important “nal” compounds, including naltrexone, naloxone, nalmefene, and nalbuphine. As demands on these APIs (active pharmaceutical ingredients) have increased, there has been a greater need for noroxymorphone to be produced more efficiently and at higher purity.
Noroxymorphone has historically been obtained by hydrolyzing dec-noroxymorphone in water with 30-40% sulfuric acid at 95 to 110° C. for 30 to 40 hours. See, e.g., “Noroxymorphone from morphine.” Wallace, Rebecca A. (Mallinckrodt, Inc., USA). Eur. Pat. Appl. EP158476 (1985). There are several problems associated with this process including: (a) the starting materials (i.e. dec-noroxymorphone) have very poor solubility; (b) the hydrolysis rate is very slow (the reaction would take 30 to 40 hours to complete); (c) the oxidative properties of the hydrolyzing agent (i.e. sulfuric acid), and prolonged heating necessary for the hydrolysis to occur results in the decomposition of the noroxymorphone product; and, (d) the overall reaction results in noroxymorphone at low yield and high impurity. A need therefore exists for a process for the conversion of opioid derivatives to key morphinan compounds useful for making analgesics and antagonists.